2015
DOI: 10.1111/jvim.12558
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Glucocorticoid Receptor Density and Binding Affinity in Healthy Horses and Horses with Systemic Inflammatory Response Syndrome

Abstract: BackgroundDysregulation of the hypothalamic‐pituitary‐adrenal (HPA) axis occurs in horses with systemic inflammatory response syndrome (SIRS). Peripheral resistance to glucocorticoids has not been investigated in horses.ObjectiveTo determine if glucocorticoid receptor (GR) function in horses can be measured using flow cytometry, and to use this information to evaluate HPA axis dynamics.AnimalsEleven healthy adult horses in parts 1 and 2. Ten horses with SIRS and 10 age and sex matched controls in part 3.Method… Show more

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Cited by 11 publications
(11 citation statements)
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“…The binding of CORT to the cytoplasmic GR causes conformational changes that allow the dissociation of heat shock regulatory proteins (HSP), allowing the GR-CORT complex to dimerize, localize in the nucleus, bind to the DNA in glucocorticoid-response elements (GRE) and regulate transcription of genes that respond to glucocorticoids [8]. However, the equine GR isoforms and their respective activities are not well characterized [9,10]. In addition, CORT itself acts through negative feedback mechanisms at the HPA axis to regulate this activity [11].…”
Section: Synthesis Of Cortisol Regulatory Mechanisms and Participatimentioning
confidence: 99%
“…The binding of CORT to the cytoplasmic GR causes conformational changes that allow the dissociation of heat shock regulatory proteins (HSP), allowing the GR-CORT complex to dimerize, localize in the nucleus, bind to the DNA in glucocorticoid-response elements (GRE) and regulate transcription of genes that respond to glucocorticoids [8]. However, the equine GR isoforms and their respective activities are not well characterized [9,10]. In addition, CORT itself acts through negative feedback mechanisms at the HPA axis to regulate this activity [11].…”
Section: Synthesis Of Cortisol Regulatory Mechanisms and Participatimentioning
confidence: 99%
“…When pituitary reserve and ability to release ACTH exceeds the corresponding capacity for adrenal production and release of cortisol, a high ACTH/cortisol ratio results indicating ACTH‐cortisol imbalance . Adrenal gland dysfunction or RAI/CIRCI is identified when cortisol release is inadequate for illness severity.…”
Section: Discussionmentioning
confidence: 99%
“…Inflammation, shock, ischemia/reperfusion injury, and SIRS are common syndromes requiring multimodal medical treatment in horses with colic. Inappropriately low basal cortisol concentrations, especially with a high ACTH/cortisol ratio could indicate pituitary‐adrenal dysregulation and possible RAI/CIRCI . This requires further investigation in severely ill horses in conjunction with assessment of ACTH‐stimulated cortisol concentrations before treatment is considered.…”
Section: Discussionmentioning
confidence: 99%
“…Clinical signs of CIRCI in the face of high circulating cortisol might result from peripheral target tissue resistance to cortisol, as is evidenced in several studies in people and rodents (Cohen and Venkatesh, 2009;Hendrix et al, 2002;Liu et al, 1993;Marik, 2009;Meduri et al, 2005). Peripheral glucocorticoid resistance has recently been described in adult horses with SIRS and is associated with increased mortality in this population (Hoffman et al, 2015).…”
Section: Introductionmentioning
confidence: 88%